Design of next-generation therapeutic IgG4 with improved manufacturability and bioanalytical characteristics
Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists betwee...
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| Veröffentlicht in: | mAbs 2020-01, Vol.12 (1), p.1829338-1829338 |
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| container_title | mAbs |
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| creator | Chen, Zhiqiang Qian, Yueming Song, Yuanli Xu, Xuankuo Tao, Li Mussa, Nesredin Ghose, Sanchayita Li, Zheng Jian |
| description | Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their manufacturing suitability. Here, we illustrate that undesirable two-peak elution profiles in cation-exchange chromatography are attributed to the S228P mutation (in IgG4 core-hinge region) intentionally designed to prevent Fab-arm exchange. A new scaffolding platform for engineering IgG4 antibodies amenable to bioprocessing and bioanalysis is proposed by introducing an "IgG1-like" single-point mutation in the hinge or CH1 region of IgG4S228P. This work offers insight into the design, discovery, and development of innovative therapeutic antibodies that are well suited for robust biomanufacturing and quality control. |
| doi_str_mv | 10.1080/19420862.2020.1829338 |
| format | Article |
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Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their manufacturing suitability. Here, we illustrate that undesirable two-peak elution profiles in cation-exchange chromatography are attributed to the S228P mutation (in IgG4 core-hinge region) intentionally designed to prevent Fab-arm exchange. A new scaffolding platform for engineering IgG4 antibodies amenable to bioprocessing and bioanalysis is proposed by introducing an "IgG1-like" single-point mutation in the hinge or CH1 region of IgG4S228P. This work offers insight into the design, discovery, and development of innovative therapeutic antibodies that are well suited for robust biomanufacturing and quality control.</description><identifier>ISSN: 1942-0862</identifier><identifier>EISSN: 1942-0870</identifier><identifier>DOI: 10.1080/19420862.2020.1829338</identifier><identifier>PMID: 33044887</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>bioanalysis ; bioprocessing ; manufacturability ; Other ; Short Communication ; single-point mutation ; therapeutic IgG4</subject><ispartof>mAbs, 2020-01, Vol.12 (1), p.1829338-1829338</ispartof><rights>2020 Bristol Myers Squibb. Published with license by Taylor & Francis Group, LLC. 2020</rights><rights>2020 Bristol Myers Squibb. 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This work offers insight into the design, discovery, and development of innovative therapeutic antibodies that are well suited for robust biomanufacturing and quality control.</description><subject>bioanalysis</subject><subject>bioprocessing</subject><subject>manufacturability</subject><subject>Other</subject><subject>Short Communication</subject><subject>single-point mutation</subject><subject>therapeutic IgG4</subject><issn>1942-0862</issn><issn>1942-0870</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>DOA</sourceid><recordid>eNp9kU9vEzEQxVcIRKvSjwDaI5cU_7dzQaACJVIlLnC2xl5v4sprB9vbNt8eh6QRveCLR2_e_Gak13VvMbrCSKEPeMkIUoJcEUSapMiSUvWiO9_rC6QkenmqBTnrLku5Q_snEZbodXdGKWJMKXnehS-u-HXs09hH91gXaxddhupT7OumVVs3V2_71fqG9Q--bno_bXO6d0M_QZxHsHXOYHzwdddDHHrjE0QIuzYEobcbyM3isi9NKG-6VyOE4i6P_0X369vXn9ffF7c_blbXn28XllNWF3LgDBSxxLglEhQEkYaSAeMlkWC5UsIh4TBDHNDAR0X4MDIqnAGztEgCvehWB-6Q4E5vs58g73QCr_8KKa815HZQcJoJhUduEGHUMDCjaTwqkSCcgsRgG-vjgbWdzeQG62LNEJ5Bn3ei3-h1uteSS0moaID3R0BOv2dXqp58sS4EiC7NRRPGkeAEI9ys_GC1OZWS3Xhag5HeB6-fgtf74PUx-Db37t8bT1NPMTfDp4PBxzHlCR5SDoOusAspjxmi9UXT_-_4AzRmvvo</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Chen, Zhiqiang</creator><creator>Qian, Yueming</creator><creator>Song, Yuanli</creator><creator>Xu, Xuankuo</creator><creator>Tao, Li</creator><creator>Mussa, Nesredin</creator><creator>Ghose, Sanchayita</creator><creator>Li, Zheng Jian</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5557-0284</orcidid><orcidid>https://orcid.org/0000-0002-1941-4145</orcidid><orcidid>https://orcid.org/0000-0001-7340-6421</orcidid><orcidid>https://orcid.org/0000-0002-5078-8049</orcidid></search><sort><creationdate>20200101</creationdate><title>Design of next-generation therapeutic IgG4 with improved manufacturability and bioanalytical characteristics</title><author>Chen, Zhiqiang ; Qian, Yueming ; Song, Yuanli ; Xu, Xuankuo ; Tao, Li ; Mussa, Nesredin ; Ghose, Sanchayita ; Li, Zheng Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-7d54a82c2be9063a627b32d11927ac5886e06e1405a0d5f825df436ebab9c07a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>bioanalysis</topic><topic>bioprocessing</topic><topic>manufacturability</topic><topic>Other</topic><topic>Short Communication</topic><topic>single-point mutation</topic><topic>therapeutic IgG4</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Zhiqiang</creatorcontrib><creatorcontrib>Qian, Yueming</creatorcontrib><creatorcontrib>Song, Yuanli</creatorcontrib><creatorcontrib>Xu, Xuankuo</creatorcontrib><creatorcontrib>Tao, Li</creatorcontrib><creatorcontrib>Mussa, Nesredin</creatorcontrib><creatorcontrib>Ghose, Sanchayita</creatorcontrib><creatorcontrib>Li, Zheng Jian</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>mAbs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Zhiqiang</au><au>Qian, Yueming</au><au>Song, Yuanli</au><au>Xu, Xuankuo</au><au>Tao, Li</au><au>Mussa, Nesredin</au><au>Ghose, Sanchayita</au><au>Li, Zheng Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design of next-generation therapeutic IgG4 with improved manufacturability and bioanalytical characteristics</atitle><jtitle>mAbs</jtitle><addtitle>MAbs</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>12</volume><issue>1</issue><spage>1829338</spage><epage>1829338</epage><pages>1829338-1829338</pages><issn>1942-0862</issn><eissn>1942-0870</eissn><abstract>Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their manufacturing suitability. Here, we illustrate that undesirable two-peak elution profiles in cation-exchange chromatography are attributed to the S228P mutation (in IgG4 core-hinge region) intentionally designed to prevent Fab-arm exchange. A new scaffolding platform for engineering IgG4 antibodies amenable to bioprocessing and bioanalysis is proposed by introducing an "IgG1-like" single-point mutation in the hinge or CH1 region of IgG4S228P. 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| source | Taylor & Francis Open Access; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | bioanalysis bioprocessing manufacturability Other Short Communication single-point mutation therapeutic IgG4 |
| title | Design of next-generation therapeutic IgG4 with improved manufacturability and bioanalytical characteristics |
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